Impedance Changes as an Indicator of Successful Skin Electroporative DNA delivery

描述（由申请人提供）：在过去的15年中，电穿孔已经发展成为一种可行的体内DNA递送方法/技术。它已被研究作为DNA疫苗、癌症治疗和代谢疾病管理的递送方法，在临床前研究中取得了很大成功。这些应用已转化为临床试验;其中大部分仍在进行中。该方法的主要复杂性是控制直流脉冲的施加，使得在靶组织中实现最大或期望的表达水平。该并发症由组织与组织之间的变化以及可能导致电脉冲治疗不足或过度治疗的其他因素引起。目前，不存在用于在施用脉冲的同时控制脉冲的施加的方法。本研究旨在探讨电阻抗作为控制电穿孔脉冲施加的真实的时间手段的可行性。该研究将首先确定由电穿孔DNA递送到皮肤引起的可测量的组织阻抗变化。这些变化将用于开发一种反馈算法，该算法将与脉冲发生器和阻抗分析仪一起工作，以控制电穿孔过程中电脉冲的应用。将在分泌蛋白的模型中测试该系统，以确定与以标准方式应用电穿孔相比，其是否可以改善所得的生物反应/表达。如果成功，这项研究将证明通过电穿孔将DNA递送到皮肤的改进方式的可行性。结果将可转化为其他组织。 公共卫生相关性：这项研究与公共卫生有关，因为结果可能导致一种改进的方法，用于提供基于DNA的癌症，代谢紊乱和免疫疗法的治疗。它也将适用于递送基于DNA的疫苗。

DESCRIPTION (provided by applicant): Electroporation has evolved, over the past 15 years, as a viable in vivo DNA delivery method/technology. It has been investigated as a delivery method for DNA vaccines, cancer treatment, and the management of metabolic diseases with much success in preclinical studies. These applications have been translated into clinical trials; most of these are still ongoing. The primary complication of this method is controlling the application of direct current pulses so that the maximum or desired level, of expression is achieved in the target tissue. The complication arises from tissue to tissue variation and other factors which can result in under treating or over treating with electric pulses. Currently, no methods exist for controlling the application of pulses while they are being administered. This proposed study is designed to investigate the feasibility of using electrical impedance as a real time means of controlling the application of electroporative pulses. The study will first identify measureable tissue impedance changes that result from electroporative DNA delivery to skin. These changes will be used to develop a feedback algorithm that will work jointly with a pulse generator and impedance analyzer to control the application of electric pulses during the electroporation process. The system will be tested in a model for a secreted protein to determine if it can improve the resulting biological response/expression compared to applying electroporation in the standard manner. If successful, this study will demonstrate the feasibility of an improved manner for delivering DNA by electroporation to the skin. The results will be translatable to other tissues. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as the results may lead to an improved method for delivering DNA based treatments for cancer, metabolic disorders, and immunotherapies. It will also be applicable for delivering DNA based vaccines.